Stability studies of hydrazide and hydroxylamine-based glycoconjugates in aqueous solution

Carbohydr Res. 2009 Feb 17;344(3):278-84. doi: 10.1016/j.carres.2008.11.007. Epub 2008 Nov 19.

Abstract

Glycoconjugates can be readily formed by the condensation of a free-reducing terminus and a strong alpha-effect nucleophile, such as a hydrazide or a hydroxylamine. Further characterization of a series of glycoconjugates formed from xylose, glucose and N-acetylglucosamine, and either p-toluenesulfonyl hydrazide or an N-methylhydroxylamine, was carried out to gain insight into the optimal conditions for the formation of these useful conjugates, and their stability. Their apparent association constants (9-74 M(-1)) at pH 4.5; as well, as rate constants for hydrolysis, at pH 4.0, 5.0 and 6.0 (37 degrees C), were determined. The half-lives of the conjugates varied between 3h and 300 days. All the compounds were increasingly stable as the pH approached neutrality. Conjugate hydrolysis rates mirrored those found for O-glycoside hydrolysis where conjugates formed from electron-rich monosaccharides hydrolyzed more rapidly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Sequence
  • Drug Stability
  • Glycoconjugates / chemistry*
  • Hydrazines / chemistry*
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Hydroxylamines / chemistry*
  • Molecular Structure
  • Solutions / chemistry
  • Water / chemistry*

Substances

  • Glycoconjugates
  • Hydrazines
  • Hydroxylamines
  • Solutions
  • Water